Successful Treatment of BK Viremia Using Reduction in Immunosuppression Without Antiviral Therapy

Saad, Ehab; Bresnahan, Barbara A.; Cohen, Eric P.; Lu, Na; Orentas, Rimas J.; Vasudev, Brahm; Hariharan, Sundaram

doi:10.1097/tp.0b013e318166cba8

Cited by 99 publications

(82 citation statements)

References 18 publications

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“…18 Moreover, it has been shown that an early diagnosis before the onset of clinically apparent nephropathy is associated with improved outcomes in this entity, which portends a poor prognosis. 2,19 The current practice in the management of PVAN involves the judicious manipulation of immunosuppression, 9,10 once the diagnosis has been confirmed by tissue biopsy. 2,7 However, insufficient decrement of immunosuppression prevents adequate disease control, whereas over reduction is associated with an increased risk of allograft rejection.…”

Section: Discussionmentioning

confidence: 99%

“…2,7 The cornerstone of PVAN management involves the reduction of immunosuppression in an attempt to restrain viral replication without inciting acute rejection. 9,10 Therefore, BKV DNA levels can guide the optimal level of immunosuppressive reduction and serve as a quantifiable surrogate marker of the course of infection. However, there appears to be limited data with regard to the presence and the level of BKV DNA in the plasma of renal transplant recipients without clinical evidence of PVAN.…”

Section: Introductionmentioning

confidence: 99%

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Quantification of BK Viral Load in Asymptomatic Renal Allograft Recipients

Chan¹,

Leung²,

Wong³

et al. 2012

Renal Failure

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Introduction: Polyoma BK virus (BKV) has recently been identified to cause renal allograft dysfunction, which manifests as polyomavirus-associated nephropathy (PVAN). However, the presence and level of BKV DNA in renal allograft patients with good and stable renal function have remained undetermined. Methods: In this prospective study, serum samples were collected from a total of 45 renal allograft recipients with serum creatinine <155 μmol/L. In 17 patients, whose duration of transplantation was under 2 years, samples were collected at 3-4-month intervals for up to 2 years after transplantation. BK viral load was quantified using quantitative polymerase chain reaction (Q-PCR). Results: The BK viral load in asymptomatic renal allograft recipients was independent of the duration of transplantation and did not correlate with allograft function. The mean (AE SD) level of viremia was 552.80 AE 1931.00 genome copies/mL, with 92.9% of patients having low levels of viremia corresponding to <1 Â 10 3 copies/mL. In contrast, patients with proven PVAN had levels in the range of 10 6 copies/mL. Conclusions: The prevailing BK viral load in asymptomatic renal allograft patients is quantifiably low. Our findings may guide optimal immunosuppressive modulation in PVAN cases, where judicious manipulation of immunosuppression is required without inciting allograft rejection.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Quantification of BK Viral Load in Asymptomatic Renal Allograft Recipients

Chan¹,

Leung²,

Wong³

et al. 2012

Renal Failure

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“…The BK polyomavirus has been proven to be one of the major viral complications in renal allografts [Andrews et al, 1988;Randhawa et al, 1999Randhawa et al, , 2005Hirsch and Steiger, 2003]. At present there is no efficient antiviral therapy available and the treatment of reactivated BKV infection is limited to reducing the immunosuppressive regimen [Almeras et al, 2008;Saad et al, 2008]. In about one-quarter to one-third of kidney transplant (KTx) patients, the virus was found in the urine, about 10-15% of BKV-infected patients reveal viremia and about 5% of BKV-infected patients develop BKVassociated nephropathy [Hirsch et al, 2002;Viscount et al, 2007].…”

Section: Introductionmentioning

confidence: 99%

Mutations in the BC‐loop of the BKV VP1 region do not influence viral load in renal transplant patients

Krautkrämer

Klein

Sommerer

et al. 2008

Journal of Medical Virology

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The reactivation and replication of the BK polyomavirus (BKV) leading to BKV-associated nephropathy (BKVAN) is one of the major complications in renal transplantation patients. BKV isolates were classified into four subtypes (I-IV) based on genotype variations within the VP1-coding region. The type-specific amino acid differences cluster within the BC-loop of the major capsid protein VP1. As demonstrated in vitro, mutations in this region also play a role in the infectivity, attachment and stability of viral particles. Therefore, we analyzed the prevalence of BC-loop mutations in isolates of kidney transplant patients and compared their viral load in the urine. The VP1 subtyping regions of BKV isolates obtained from urine samples of 45 renal transplant patients were sequenced. The phylogenetic analysis of these sequences revealed that subtype I (66.67%) is the most prevalent genotype. The remaining isolates belong to subtype IV (33.33%). A high frequency of changes to specific amino acids within the BC-loop was identified among the BKV isolates from renal transplant patients. Patients with BKVAN exhibited a higher viral replication than patients without nephropathy. Although titers of isolates of subtype I were higher than titers of subtype IV isolates, the difference did not reach statistical significance. In addition, amino acid changes in the BC-loop did not influence the viral load and the incidence of BKVAN. These in vivo results demonstrate that high replication rates which serve as a predictive marker for BKVAN are not caused by altered receptor binding or affinity via mutated BC-loops.

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“…To date, there is no established consensus on the treatment of BK viremia and nephropathy. However, reduction in immunosuppression is fundamental to clearance of the virus (1,2,5,10). Alternative treatment options include cidofovir, intravenous Ig, fluoroquinolones, and leflunomide (1,5,11).…”

Section: Introductionmentioning

confidence: 99%

Leflunomide Efficacy and Pharmacodynamics for the Treatment of BK Viral Infection

Krisl¹,

Taber²,

Pilch³

et al. 2012

Clinical Journal of the American Society of Nephrology

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SummaryBackground and objectives BK virus is an infection in kidney transplantation patients jeopardizing graft survival. Unfortunately, there is no consensus on treatment of BK viremia and nephropathy. Leflunomide has been studied for the treatment of BK viremia and nephropathy, but there are limited data on the utility of leflunomide therapeutic drug monitoring. This study aimed to determine if a pharmacodynamic relationship exists between BK viral load reduction and leflunomide metabolite, A77 1726, serum concentrations.Design, setting, participants, & measurements This study was a retrospective, single-center, longitudinal analysis of patients identified with BK viremia with or without nephropathy. Patients were grouped according to whether they received leflunomide. All BK viral PCR and A77 1726 concentrations were analyzed to determine pharmacodynamics, and were correlated with clinical outcomes.Results Of 76 patients identified, 52 received leflunomide therapy and 24 did not. Patients who received leflunomide were further analyzed according to A77 1726 concentrations and BK clearance; there was no difference in BK clearance. There was a lack of correlation between A77 1726 concentrations and log change in BK viral PCR concentration. Multivariate analysis demonstrated that mycophenolate mofetil discontinuation, BK viremia without nephropathy, and mean BK viral load were significantly associated with BK viral clearance; leflunomide use lacked this association.Conclusions Pharmacodynamic analysis revealed no association between A77 1726 concentrations and BK viral PCR reductions. Multivariate analysis demonstrated that leflunomide therapy was not associated with BK viral clearance. Randomized studies are needed to determine the utility of leflunomide for BK viremia and nephropathy.

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Successful Treatment of BK Viremia Using Reduction in Immunosuppression Without Antiviral Therapy

Cited by 99 publications

References 18 publications

Quantification of BK Viral Load in Asymptomatic Renal Allograft Recipients

Quantification of BK Viral Load in Asymptomatic Renal Allograft Recipients

Mutations in the BC‐loop of the BKV VP1 region do not influence viral load in renal transplant patients

Leflunomide Efficacy and Pharmacodynamics for the Treatment of BK Viral Infection

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